Tripdiolide (C.sub.20 H.sub.24 O.sub.7), triptolide (C.sub.20 H.sub.24 O.sub.6) and triptonide (C.sub.20 H.sub.22 O.sub.6) were first isolated from the roots of T. wilfordii Hook F by Kupchan et al, J. Am. Chem. Soc., vol. 94 (1972) at 7194-7195, herein incorporated by reference. The amounts of tripdiolide and triptolide isolated from this natural source were about 0.001% by weight of the plant dry weight.
Kupchan et al, In U.S. Pat. No. 4,005,108, have further described the isolation of minute amounts of triptonide, triptolide and tripdiolide from the ground roots of T. wilfordii Hook F.
Celastrol or tripterine is a red pigment isolated from the roots of both T. wilfordii and Celastrus scandens, as disclosed by Schechter et al, J. Am. Chem. Soc., vol. 64 (1942) at 182-183, incorporated herein be reference. Celastrol can be converted by reaction with diazomethane, in a reaction followed by column chromatography, to a methyl ester (pristimerin) m.p. 214.degree.-217.degree., C.sub.30 H.sub.40 O.sub.4.
Celastrol is a member of a group of triterpene-type compounds called quinone-methides. Closely related compounds, tingenone and pristimerin, have been isolated from Maytenus chuchuhuasca Raymond Hamet, a plant which has been used in Ecuador for skin cancer treatment (see P. Martinod, A. Paredes, F. D. Monache and G. B. Marini-Bettolo, Phytochemistry, Vol. 15 (1976) at 562-563.
The isolation and characterization of some related quinone-methides, including pristimerin, has been reported by Monache et al, J. Chem. Soc. Perkin I (1979) at 3127-3131. Some of these compounds also have anti-neoplastic effect.
In view of the promising anti-leukemic activity of tripdiolide and triptolide and of the anti-tumor activity of celastrol, it will be apparent that there is a need for synthetic routes producing reasonable amounts of these materials.
It is an object of this invention to provide a process for selective production, in reasonable yields, of tripdiolide, triptolide and celastrol by plant cell culture.